title: Insights into soluble guanylyl cyclase activation derived from improved heme-mimetics.
abstract: Recently, the structure of BAY 58-2667 bound to the Nostoc sp. H-NOX domain was published. On the basis of this structural information, we designed BAY 58-2667 derivatives and tested their effects on soluble guanylyl cyclase (sGC) activity. Derivative 20 activated sGC 4.8-fold more than BAY 58-2667. Co-crystallization of 20 with the Ns H-NOX domain revealed that the increased conformational distortion at the C-terminal region of αF helix containing 110-114 residues contributes to the higher activation triggered by 20.
authors.affiliation: Institut für Organische Chemie, Universität Leipzig, Leipzig, Germany.
authors.forename: Margarete von Wantoch
authors.initials: MVW
authors.lastname: Rekowski
authors.affiliation: Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Vijay
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Pharmacy, Laboratory of Molecular Pharmacology, University of Patras, Greece.|"G.P.Livanos-M.Simou" Laboratories, 1st Department of Critical Care Medicine and Pulmonary Services, Evangelismos Hospital, University of Athens School of Medicine, Athens, Greece.
authors.forename: Zongmin
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Institut für Organische Chemie, Universität Leipzig, Leipzig, Germany.
authors.forename: Johann
authors.initials: J
authors.lastname: Moschner
authors.affiliation: Department of Pharmacy, Laboratory of Molecular Pharmacology, University of Patras, Greece.
authors.forename: Antonia
authors.initials: A
authors.lastname: Marazioti
authors.affiliation: Institut für Organische Chemie, Universität Leipzig, Leipzig, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Bantzi
authors.affiliation: Department of Pharmacy, Laboratory of Molecular Pharmacology, University of Patras, Greece.
authors.forename: Georgios A
authors.initials: GA
authors.lastname: Spyroulias
authors.affiliation: Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Focco
authors.initials: F
authors.lastname: van den Akker
authors.affiliation: Institut für Organische Chemie, Universität Leipzig, Leipzig, Germany.
authors.forename: Athanassios
authors.initials: A
authors.lastname: Giannis
authors.affiliation: Department of Pharmacy, Laboratory of Molecular Pharmacology, University of Patras, Greece.
authors.forename: Andreas
authors.initials: A
authors.lastname: Papapetropoulos
mesh_terms: D001565:Benzoates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism*; D006418:Heme / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008968:Molecular Conformation / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D046937:Nostoc / Q000201:enzymology; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism*; D000071756:Soluble Guanylyl Cyclase; D013329:Structure-Activity Relationship
chemical_list: D001565:Benzoates; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; C480588:BAY 58-2667; D006418:Heme; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase